The heat shock response protects cells from damage caused by environmental and physiological stress, and is involved in a wide range of pathophysiological conditions, such as breast cancer, heart disease, and aging. Production of heat shock proteins is mainly controlled at the transcriptional level, and heat shock genes are activated by heat shock transcription factors (HSFs). HSFs contain highly conserved regions among eukaryotes, particularly at the DNA-binding and oligomerization domains. HSFs specifically bind DNA as homotrinfets, though strong cooperativity between trimers occurs, and this cooperativity may be mechanistically important for controlling differential gene expression. Previous attempts to crystallize an HSF trimer bound to DNA had failed, possibly because of the presence of multiple complexes formed by cooperative binding. HSF will first be studied by mutagenesis of residues believed to be critical in cooperative interactions, followed by DNA binding assays. Elimination of cooperativity will allow attempts for crystallographic analysis of a HSF trimer bound to DNA. Solving this structure will increase the understanding of DNA binding and trimerization by a unique and complex protein involved in broad cellular processes.